Relationship Between Clozapine and Non-Hematological Malignant Tumors: A Pharmacovigilance Analysis Using the FDA Adverse Event Reporting System Database.

Background and objectives: Clozapine shows higher efficacy against treatment-resistant schizophrenia than other antipsychotics. This study aimed to investigate whether clozapine is associated with the risk of non-hematological malignant tumors, utilizing the US Food and Drug Administration (FDA) Adverse Event Report System (FAERS) database.

Methods: The records from the first quarter of 2004 to the third quarter of 2012 were used for disproportionality analysis, and patients who developed non-hematological malignant tumors were identified by the Standardized Medical Dictionary for Regulatory Activities Queries (SMQ).

Results: Of the 3,641,281 patients with 12,401,586 reports of adverse drug events, 151,904 reports belonged to non-hematological malignant tumors (SMQ). We identified 1668 reports of non-hematological malignant tumors (SMQ) in clozapine users, and the reporting odds ratio (ROR) was calculated to be 1.28 (95% confidence interval (CI): 1.22-1.34). ROR (95% CI) for the relationship between clozapine and the risk of testis cancer was calculated as 10.94 (6.99-17.12), 9.87 (7.42-13.15) for gastrointestinal carcinoma, 7.48 (5.57-10.05) for metastatic lung cancer, 6.71 (4.52-9.97) for throat cancer, 6.12 (4.56-8.21) for metastases to the spine, 5.97 (5.30-6.72) for lung malignant neoplasm, 5.07 (3.69-6.95) for esophageal carcinoma, 1.88 (1.43-2.47) for colon cancer, and 1.65 (1.24-2.21) for metastases to the liver. Colon cancer, esophageal carcinoma, and throat cancer were predominantly reported in males, and metastases to the spine and liver were in females.

Conclusion: This study detected signals indicating a relationship between clozapine and certain non-hematological malignant tumors, utilizing the FAERS database. Despite the database relying on spontaneous reporting, the current results justify further investigation.